Fine-Needle Aspiration is the Most Appropriate Next Step
For a 2 cm firm, non-tender, mobile thyroid nodule on ultrasound, proceed directly to ultrasound-guided fine-needle aspiration biopsy—do not wait 4-6 weeks. 1, 2
Rationale for Immediate FNA
Any thyroid nodule ≥1 cm warrants FNA regardless of ultrasound features, because size alone is a critical determinant for malignancy risk, with approximately 5-15% of thyroid nodules harboring cancer. 1, 3
A 2 cm nodule exceeds the threshold where observation is acceptable—current guidelines from the American College of Surgeons and National Comprehensive Cancer Network recommend evaluation of nodules larger than 2 cm even without suspicious features due to increased malignancy risk. 1
The clinical characteristics described (firm, mobile, non-tender) do not exclude malignancy—palpation alone cannot reliably differentiate benign from malignant thyroid nodules, and reliance on physical examination may delay diagnosis. 1
Why Waiting 4-6 Weeks is Inappropriate
Short-term observation (4-6 weeks) is appropriate only for suspected infectious or inflammatory thyroid conditions or post-procedural changes—it is not indicated for solid thyroid nodules such as the 2 cm lesion described. 1
Delaying FNA provides no diagnostic benefit and may postpone the detection of malignancy, as most thyroid cancers occur in patients with normal thyroid function and unremarkable clinical presentations. 1, 4
Procedural Approach
Ultrasound-guided FNA is preferred over palpation-guided biopsy because it provides real-time needle visualization, improves sampling accuracy, and yields higher diagnostic certainty with approximately 95% accuracy. 1, 5
The cytology specimen should be categorized according to the Bethesda System for Reporting Thyroid Cytopathology, which stratifies nodules by malignancy risk (1-3% for Bethesda II benign, up to 97% for mutation-positive nodules) to guide subsequent management. 1, 2
Additional Diagnostic Considerations
Measure serum TSH before FNA, as higher TSH levels are associated with increased risk of differentiated thyroid cancer, and suppressed TSH may indicate an autonomously functioning nodule that requires radionuclide scanning. 1, 2
Consider measuring serum calcitonin as part of the diagnostic workup to screen for medullary thyroid cancer, which has higher sensitivity than FNA alone and detects 5-7% of thyroid cancers that FNA may miss. 1, 2
Perform comprehensive neck ultrasonography to assess for suspicious cervical lymphadenopathy, extrathyroidal extension, and additional nodule characteristics (hypoechogenicity, microcalcifications, irregular margins, absence of peripheral halo, central hypervascularity). 1, 2
Management Based on FNA Results
Bethesda II (benign): Surveillance with repeat ultrasound at 12-24 months, as malignancy risk is only 1-3%. 1
Bethesda III/IV (indeterminate): Consider molecular testing for BRAF, RAS, RET/PTC, and PAX8/PPARγ mutations to refine malignancy risk and guide surgical decision-making. 1
Bethesda V/VI (suspicious or malignant): Immediate referral to an endocrine surgeon for total or near-total thyroidectomy with pre-operative assessment of lymph node compartments. 1, 2
Nondiagnostic sample: Repeat FNA under ultrasound guidance, as inadequate samples occur in 5-20% of cases. 1, 5
Critical Pitfalls to Avoid
Do not rely on thyroid function tests (TSH, T3, T4) alone for malignancy assessment, as most thyroid cancers present with normal thyroid function. 1
Do not perform radionuclide scanning in euthyroid patients to determine malignancy risk—ultrasound features are far more predictive, and scanning does not substitute for FNA. 1, 4
A reassuring FNA should not override worrisome clinical findings, as false-negative results occur in up to 11-33% of cases—if clinical suspicion remains high despite benign cytology, consider repeat FNA or surgical consultation. 1, 2